The prognostic value and immunological role of CD44 in pan-cancer study

Abstract

To investigate the correlation between cluster of differentiation-44 (CD44) expression and immunotherapy response and identify its possible predictive value in pan-cancer. Datasets of 33 cancer types from The Cancer Genome Atlas (TCGA) database were applied to investigate the relationship of CD44 expression with prognosis, tumor mutational burden (TMB), and microsatellite instability (MSI), and determine its potential prognostic value in pan-cancer. Patients were split into high-risk and low-risk cancer groups based on the survival outcomes of various cancer types. Additionally, the underlying mechanisms of CD44 in the tumor microenvironment (TME) were analyzed using ESTIMATE and CIBERSORT algorithms and Gene Set Enrichment Analysis (GSEA). Subsequently, the biological role of CD44 at single-cell level was investigated using CancerSEA database. Variable expression levels of CD44 between tumor and adjacent normal tissues were identified in pan-cancer datasets, further survival analysis revealed that CD44 expression was associated with multiple clinical annotations and survival indicators. Besides, the expression of CD44 was significantly associated with TMB and MSI in 10 types and 6 types of cancer, respectively, indicating it could be exploited as a potential biomarker predicting immunotherapy outcomes. Meanwhile, CD44 could influence several crucial immune cell-related pathways. and the results revealed by CancerSEA database denoted the correlation of CD44 with malignant phenotype and functional states, further indicating it can serve as a potential therapeutic target in cancer management. Our study demonstrated that CD44 shows great promise as a prognostic biomarker in numerous cancers, which will assist in developing new strategies in cancer management.